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Article Dans Une Revue eLife Année : 2020

Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation

Résumé

Neuroligins (Nlgns) are adhesion proteins mediating trans-synaptic contacts in neurons. However, conflicting results around their role in synaptic differentiation arise from the various techniques used to manipulate Nlgn expression level. Orthogonally to these approaches, we triggered here the phosphorylation of endogenous Nlgn1 in CA1 mouse hippocampal neurons using a photoactivatable tyrosine kinase receptor (optoFGFR1). Light stimulation for 24 hr selectively increased dendritic spine density and AMPA-receptor-mediated EPSCs in wild-type neurons, but not in Nlgn1 knockout neurons or when endogenous Nlgn1 was replaced by a nonphosphorylatable mutant (Y782F). Moreover, light stimulation of optoFGFR1 partially occluded LTP in a Nlgn1-dependent manner. Combined with computer simulations, our data support a model by which Nlgn1 tyrosine phosphorylation promotes the assembly of an excitatory post-synaptic scaffold that captures surface AMPA receptors. This optogenetic strategy highlights the impact of Nlgn1 intracellular signaling in synaptic differentiation and potentiation, while enabling an acute control of these mechanisms.

Domaines

Neurobiologie
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Dates et versions

hal-03025902 , version 1 (26-11-2020)

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Mathieu Letellier, Matthieu Lagardère, Béatrice Tessier, Harald Janovjak, Olivier Thoumine. Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation. eLife, 2020, 9, ⟨10.7554/elife.52027⟩. ⟨hal-03025902⟩

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